TY - JOUR
T1 - Compensatory intestinal immunoglobulin response after vancomycin treatment in humans
AU - Scheithauer, Torsten P. M.
AU - Bakker, Guido J.
AU - Winkelmeijer, Maaike
AU - Davids, Mark
AU - Nieuwdorp, Max
AU - van Raalte, Daniël H.
AU - Herrema, Hilde
N1 - Funding Information: DHvR was supported by a fellowship of the Dutch Diabetes Foundation and EU Marie Curie Program. Publisher Copyright: © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021
Y1 - 2021
N2 - Intestinal immunoglobulins (Ig) are abundantly secreted antibodies that bind bacteria and bacterial components in the gut. This binding is considered to accelerate bacterial transit time and prevent the interaction of potentially immunogenic compounds with intestinal immune cells. Ig secretion is regulated by alterations in gut microbiome composition, an event rarely mapped in an intervention setting in humans. Here, we determined the intestinal and systemic Ig response to a major intervention in gut microbiome composition. Healthy humans and humans with metabolic syndrome received oral vancomycin 500 mg four times per day for 7 days. Coinciding with a vancomycin-induced increase in Gram-negative bacteria, fecal levels of the immunogenic bacterial components lipopolysaccharide (LPS) and flagellin drastically increased. Intestinal antibodies (IgA and IgM) significantly increased, whereas peripheral antibodies (IgG, IgA, and IgM) were mostly unaffected by vancomycin treatment. Bacterial cell sorting followed by 16S rRNA sequencing revealed that the majority of Gram-negative bacteria, including opportunistic pathogens, were IgA-coated after the intervention. We suggest that the intestinal Ig response after vancomycin treatment prevents the intrusion of pathogens and bacterial components into systemic sites.
AB - Intestinal immunoglobulins (Ig) are abundantly secreted antibodies that bind bacteria and bacterial components in the gut. This binding is considered to accelerate bacterial transit time and prevent the interaction of potentially immunogenic compounds with intestinal immune cells. Ig secretion is regulated by alterations in gut microbiome composition, an event rarely mapped in an intervention setting in humans. Here, we determined the intestinal and systemic Ig response to a major intervention in gut microbiome composition. Healthy humans and humans with metabolic syndrome received oral vancomycin 500 mg four times per day for 7 days. Coinciding with a vancomycin-induced increase in Gram-negative bacteria, fecal levels of the immunogenic bacterial components lipopolysaccharide (LPS) and flagellin drastically increased. Intestinal antibodies (IgA and IgM) significantly increased, whereas peripheral antibodies (IgG, IgA, and IgM) were mostly unaffected by vancomycin treatment. Bacterial cell sorting followed by 16S rRNA sequencing revealed that the majority of Gram-negative bacteria, including opportunistic pathogens, were IgA-coated after the intervention. We suggest that the intestinal Ig response after vancomycin treatment prevents the intrusion of pathogens and bacterial components into systemic sites.
KW - Immunoglobulin
KW - LPS
KW - flagellin
KW - gut microbiota
KW - vancomycin
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85099955030&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/33475461
UR - http://www.scopus.com/inward/record.url?scp=85099955030&partnerID=8YFLogxK
U2 - https://doi.org/10.1080/19490976.2021.1875109
DO - https://doi.org/10.1080/19490976.2021.1875109
M3 - Article
C2 - 33475461
SN - 1949-0976
VL - 13
SP - 1
EP - 14
JO - Gut Microbes
JF - Gut Microbes
IS - 1
ER -